HMG-CoA Reductase Inhibitors Statins

This category includes atorvastatin (Lipitor), fluvas-tatin (Lescol), lovastatin (Mevacor), pravastatin (Prava-chol), and simvastatin (Zocor) (Table 25-2). These drugs, known commonly as statins, are characterized by their ability to inhibit an enzyme known as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.96 This enzyme catalyzes one of the early steps of cholesterol synthesis, and drugs that inhibit HMG-CoA reductase decrease cholesterol produc- 

The HMG-CoA reductase inhibitors therefore improve several aspects of the plasma lipid profile. These agents may produce several favorable effects that are independent of their ability to affect plasma lipid levels.9,96 It appears that certain by-products of cholesterol metabolism act directly or influence the production of other chemical signals that adversely affect cellular function in various tissues.9 Increased production of these by-products could therefore influence a variety of pathological conditions. By controlling the production of these by-products, statins may produce a wide range of beneficial effects in addition to their ability to improve plasma lipids. 

Statins are helpful in decreasing morbidity and mortality in people with high cholesterol, as well as individuals who have normal cholesterol but other risk factors for cardiovascular disease.66 It is estimated that these drugs decrease the risk of a major cardiac event by approximately 30 to 35 percent, although the benefits depend on the extent that cholesterol is reduced and the influence of other risk factors.91,95,126 Nonetheless, statins are now regarded as a mainstay in treating cardiovascular disease, and efforts are underway to expand the use of these medications and to explore the 

Generic Name Atorvastatin Trade Name(s) Lipitor Dosage 10-80 mg once each day Primary Effect Decreases total cholesterol and plasma LDL-C may also decrease triglycerides and increase HDL-C somewhat 

Cholestyramine Questran 4 g 2-6 times each day before meals and at bedtime Decreases total cholesterol and LDL-C 

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HMG-CoA reductase inhibitors (statins). This effect has been suggested to account for some of the side effects of statins like myositis or rhabdomyolysis. 

HMG-CoA-Reductase Inhibitors. Figure 1 Mechanism of action of statins - cholesterol synthesis pathway. The conversion of acetyl CoA to cholesterol in the liver. The step of cholesterol biosynthesis inhibited by HMG-CoA reductase inhibitors (statins) is shown. 

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

The NKF suggests that CKD should be classified as a coronary heart disease (CHD) risk equivalent and the goal LDL-C level should be below 100 mg/dL in all patients with CKD.22 The most frequently used agents for the treatment of dyslipidemias in patients with CKD are the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ( statins ) and the fibric acid derivatives. However, other treatments have been studied in patients with CKD and should be considered if first-line therapies are contraindicated. 

Interest in the role of HMG-CoA reductase inhibitors (statins) in the treatment of osteoporosis came from boneforming properties seen in animal studies. However, controlled clinical trials are needed. 

Cardiovascular Keep doses of NSAIDs and glucocorticoids low, consider initiation of folic acid to reduce homocysteine level elevations induced by methotrexate, consider initiation of low-dose aspirin and/or HMG-CoA reductase inhibitors (statins), and encourage smokers to discontinue tobacco use and assist with the development of a tobacco-cessation plan.11,12... 

Additional agents, including selenium, folic acid, and HMG-CoA reductase inhibitors (statins), show promise as chemopreventive agents in colon cancer, and preliminary and confirmatory studies evaluating their effectiveness have been completed or are ongoing, although none of these agents have been approved for the prevention of colon cancer.46... 

Schonbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors statins as antiinflammatory agents Circulation 2004 109(21 Suppl 1) II18-II26. 

HMG-CoA reductase inhibitors (Statins), 5 137, 138-140t, 142-143 HMX (High Melting eXplosive octahydro-1,3,5,7- tetranitro-l,3,5,7-tetrazocine), 70 735-736... 

Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtlscherer S, Martin H, Zeiher AM. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001 108 391-397. 

Fig. 8. Most important steps in the biosynthesis of cholesterol. The reduction of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) to yield mevalonic acid is an important rate-limiting step and also the site of attack of the HMG-CoA-reductase inhibitors (statins).

Lowering LDL cholesterol is highly effective if LDL is higher than 130 mg/dl and in suspected coronary artery disease (CAD) patients. A 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) will be the first choice, and target LDL will be less than 100 mg/dl. LDL levels between 100-129 mg/dl will also be advantageous to be treated. Other than statins, cholestylamine, forate or other types will also be used. 

HMG-CoA Reductase Inhibitors Statins inhibit HMG-CoA reductase, the enzyme synthesizing mevalonic acid (a key step in cholesterol biosynthesis). These drugs are indicated to treat hypercholesterolemia and to reduce LDL cholesterol. 

Wang E, Casciano CN, Clement RP, Johnson WW. HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharm Res 2001 18(6) 800-806. 

Today HMG-CoA reductase inhibitors (statins) account for the large majority of prescriptions for lipid-lowering drugs in most countries. As discussed in a subsequent section of this chapter, the widespread acceptance of this drug class is due not only to excellent efficacy and tolerability but also to the publication of several very large intervention trials, which have unequivocally demonstrated the effectiveness of the first three members of the class—lovastatin, simvastatin, and pravastatin—in reducing coronary morbidity and mortality. 

The HMG-CoA reductase inhibitors (Statins like simvastatin, lovastatin, pravastatin, fluvastatin, etc.) inhibit the enzyme and thereby decrease the hepatic cholesterol synthesis and increase the synthesis of LDL receptors causing increased clearance of LDL and a reduced concentration of LDL cholesterol in plasma. HMG-CoA reductase inhibitors are used to treat elevated LDL which also causes a small reduction in plasma triglycerides and an increase in HDL cholesterol. 

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